pghm-1
C. elegans
putative peptidylglycine alpha-hydroxylating monooxygenase 1
What the model saw
Gene: pghm-1 Organism: Caenorhabditis elegans Known functions: putative peptidylglycine alpha-hydroxylating monooxygenase 1. catalytic activity. copper ion binding. monooxygenase activity. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced ascorbate as one donor, and incorporation of one atom of oxygen. peptidylglycine monooxygenase activity.
View unredacted entry
putative peptidylglycine alpha-hydroxylating monooxygenase 1. catalytic activity. copper ion binding. monooxygenase activity. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced ascorbate as one donor, and incorporation of one atom of oxygen. peptidylglycine monooxygenase activity.
Solver output
pghm-1 encodes a putative peptidylglycine alpha-hydroxylating monooxygenase (PHM), a copper-dependent oxidoreductase that catalyzes the first step in C-terminal alpha-amidation of neuropeptides and peptide hormones. This amidation is essential for the bioactivity of many secreted signaling peptides (e.g., neuropeptides), placing pghm-1 squarely in intercellular communication via peptidergic signaling. In C. elegans, neuropeptide signaling networks are complex and can both promote and oppose longevity depending on which peptides are activated — for example, insulin-like peptides processed through amidation can be pro- or anti-aging. Because the specific downstream peptide substrates of pghm-1 in C. elegans are not well characterized, and amidated neuropeptides can have opposing effects on lifespan (e.g., activating DAF-2/insulin signaling vs. other pathways), the net longevity influence cannot be confidently assigned from molecular function alone.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted "unclear" while the ground truth is "anti_longevity." The model's reasoning about neuropeptide amidation and intercellular communication is plausible mechanistically, but it failed to commit to a direction. The model acknowledged the role of pghm-1 in neuropeptide processing but argued that the net longevity effect was ambiguous due to potentially opposing downstream effects. In reality, pghm-1 is classified as anti-longevity, meaning its loss likely extends lifespan. The model's mechanism class of "altered_intercellular_communication" is reasonable given the neuropeptide processing role, but the failure to predict the correct direction (anti_longevity) is a significant error. The model was appropriately uncertain given limited specific data, but the ground truth shows a clear anti-longevity classification.
Raw API responses
solver
{
"reasoning": "pghm-1 encodes a putative peptidylglycine alpha-hydroxylating monooxygenase (PHM), a copper-dependent oxidoreductase that catalyzes the first step in C-terminal alpha-amidation of neuropeptides and peptide hormones. This amidation is essential for the bioactivity of many secreted signaling peptides (e.g., neuropeptides), placing pghm-1 squarely in intercellular communication via peptidergic signaling. In C. elegans, neuropeptide signaling networks are complex and can both promote and oppose longevity depending on which peptides are activated — for example, insulin-like peptides processed through amidation can be pro- or anti-aging. Because the specific downstream peptide substrates of pghm-1 in C. elegans are not well characterized, and amidated neuropeptides can have opposing effects on lifespan (e.g., activating DAF-2/insulin signaling vs. other pathways), the net longevity influence cannot be confidently assigned from molecular function alone.",
"confidence": 0.35,
"key_pathways": [
"neuropeptide amidation",
"peptidergic intercellular signaling",
"copper-dependent oxidoreductase activity"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model's reasoning about neuropeptide amidation and intercellular communication is plausible mechanistically, but it failed to commit to a direction. The model acknowledged the role of pghm-1 in neuropeptide processing but argued that the net longevity effect was ambiguous due to potentially opposing downstream effects. In reality, pghm-1 is classified as anti-longevity, meaning its loss likely extends lifespan. The model's mechanism class of \"altered_intercellular_communication\" is reasonable given the neuropeptide processing role, but the failure to predict the correct direction (anti_longevity) is a significant error. The model was appropriately uncertain given limited specific data, but the ground truth shows a clear anti-longevity classification.",
"failure_mode": "appropriately_uncertain",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}